We have characterized nuclear molecular events during the activation of human T lymphocytes. The c-myc oncogene, the interleukin-2 (IL-2) growth factor and the IL-2 receptor gene are known to be induced early during the activation of T cells. Chromatin structure analyses and some DNA mediated transfection experiments have allowed us to identify several regulatory elements of these genes. In the case of the IL-2 gene, we have identified an element likely to be involved in the transmission of the extracellular activation signal. Along the same lines, a model system has been developed to study the effect of differentiation at the nuclear level. The promyelocytic leukemia cell line HL60 can be differentiated terminally in vitro. Concomitantly, the expression of the c-myc oncogene is downregulated. We have identified two distinct mechanisms to transcriptionally downmodulate c-myc, an early and a later acting one; the latter one is associated with dramatic chromatin changes of the c-myc gene. We have initiated also more broadly based studies directed at the activation process of T cells. cDNA libraries have been made from activated peripheral blood T cells and have been used to identify genes which are specifically and immediately induced upon mitogenic stimulation. Several of these genes appear to be regulated in a manner analogous to that of the c-fos oncogene. These libraries are utilized also to identify genes coding for lymphokines which are elaborated by these T cells after stimulation. To clone the well-characterized B cell growth factor (BCGF), we have also made libraries from a B cell tumor which expresses BCGF constitutively. Furthermore, we have initiated the cloning of the recently identified receptor for this growth factor by creating a cDNA library from an Epstein-Barr virus transformed B cell line expressing a relatively high number of these receptors. Lastly, we have used the purified BCGF to study its molecular effects on B cells. Specifically, we have determined that the c-myc oncogene is induced rapidly even on small B cells, which require a signal in addition to BCGF for proliferation.